Drug Metabolism

When a foreign compound enters the bloodstream, the body attempts to remove it using different metabolic processes. All compounds that enter the bloodstream from the gastrointestinal tract first pass through the liver, the site of most xenobiotic metabolism. The liver expresses a wide variety of enzymes that chemically alter blood-borne toxins and chemicals. Active transport or carrier proteins import xenobiotics or drugs into and export metabolites out of liver cells. Enzymes involved in phase I metabolism (cytochrome P450 enzymes) first modify these chemicals with polar functional groups using reactions such as oxidation, reduction, and hydrolysis. Enzymes involved in phase II metabolism (transferases and hydrolases) next conjugate these newly polar metabolites and electrophilic xenobiotics with inactive groups such as glutathione, glucuronic acid, amino acids, or sulfonates. Ultimately, this process generates larger and more polar metabolites than the original xenobiotic, making them easier to excrete. Drug metabolism dysregulation is implicated in many disease states including cancer, addiction, and metabolic diseases. ...

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When a foreign compound enters the bloodstream, the body attempts to remove it using different metabolic processes. All compounds that enter the bloodstream from the gastrointestinal tract first pass through the liver, the site of most xenobiotic metabolism. The liver expresses a wide variety of enzymes that chemically alter blood-borne toxins and chemicals. Active transport or carrier proteins import xenobiotics or drugs into and export metabolites out of liver cells. Enzymes involved in phase I metabolism (cytochrome P450 enzymes) first modify these chemicals with polar functional groups using reactions such as oxidation, reduction, and hydrolysis. Enzymes involved in phase II metabolism (transferases and hydrolases) next conjugate these newly polar metabolites and electrophilic xenobiotics with inactive groups such as glutathione, glucuronic acid, amino acids, or sulfonates. Ultimately, this process generates larger and more polar metabolites than the original xenobiotic, making them easier to excrete. Drug metabolism dysregulation is implicated in many disease states including cancer, addiction, and metabolic diseases.